It’s well known how psilocybin works at the molecular level, but what does this mean for brain function in general? Based on the external manifestations of the effects of psychoactive substances on the psyche, one can only speculate about the physiological mechanisms of their effects. A series of long-term studies using functional magnetic resonance imaging helped to see the real picture. It turns out that psilocybin is considered a “spiritual regenerative” drug for good reason: it causes a radical restructuring of the large-scale brain network responsible for introspection and memorization.

People’s attitudes toward hallucinogens range from “a relatively safe recreational substance with potential therapeutic effects” to “a beginner’s drug with all its consequences.” Such uncertainty has largely hindered research into the effects of psilocybin and similar compounds on the human body. However, before the height of the war on drugs, scientists had established that a number of psychoactive substances had good safety profiles and had enormous potential as drugs for treating mental disorders.

But half a century ago, humanity did not have the tools to see the true extent of the positive (or negative) effects that psychedelics can have on the brain. Half a century later, such tools, especially functional magnetic resonance imaging (fMRI), emerged. With its help, American researchers were able to determine exactly how psilocybin works on the scale of the entire human brain.

The study involved seven volunteers who received a high dose of the drug intravenously — 25 milligrams, two and a half times the minimum dose to achieve a psychedelic effect (a typical recreational dose is estimated to be 10 to 50 milligrams). Each subject underwent an average of 18 fMRI sessions over six weeks: several times during the three weeks before taking psilocybin, once during the psychedelic experience, and several times during the three weeks after. Four volunteers agreed to repeat the experiment in the same manner within a year.

During the procedure, tomography was used to determine the functional connectivity of the brain structures of the volunteers while they performed standardized tasks. The scientists were interested in what large-scale brain networks were revealed under the influence of psilocybin.

It turned out that the functioning of the network called the standard mode is most altered. It includes important areas of the prefrontal cortex of the brain and is activated when a waking person is resting and focused on introspective tasks: dreams, imagining the future, memories, self-analysis (reflection).

When psilocybin starts to work, this large-scale brain network becomes severely disorganized. The effect lasts for several hours and is three times stronger and longer-lasting than the effect caused by the control methylphenidate (Ritalin). Normally, the picture of any large-scale brain network is individual. As the researchers note, it can actually be used as a fingerprint. But under psilocybin, it was difficult to distinguish the brains of one volunteer from another: The drug literally “reset” them to a blank slate.

After a while, this effect wore off, and the default mode brain network re-individualized, but it was much more dispersed than before taking psilocybin. The functional connectivity of the subjects’ brains was rebuilt.

Scientific study that includes a detailed description of the experiment, its methodology, and its results.
published in the magazine Natureunder review. The authors urge against jumping to conclusions about the positive effects of psilocybin. They believe that their research provides a solid foundation for further studies of the mechanisms of action of psychoactive substances on the human brain. This promises either wider use in the treatment of mental disorders or the creation of new drugs that more effectively affect targeted large-scale brain networks. Or perhaps both.